Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
, 7, 27

TNF-alpha and Neuropathic Pain--A Review


TNF-alpha and Neuropathic Pain--A Review

Lawrence Leung et al. J Neuroinflammation.


Tumor necrosis factor alpha (TNF-alpha) was discovered more than a century ago, and its known roles have extended from within the immune system to include a neuro-inflammatory domain in the nervous system. Neuropathic pain is a recognized type of pathological pain where nociceptive responses persist beyond the resolution of damage to the nerve or its surrounding tissue. Very often, neuropathic pain is disproportionately enhanced in intensity (hyperalgesia) or altered in modality (hyperpathia or allodynia) in relation to the stimuli. At time of this writing, there is as yet no common consensus about the etiology of neuropathic pain - possible mechanisms can be categorized into peripheral sensitization and central sensitization of the nervous system in response to the nociceptive stimuli. Animal models of neuropathic pain based on various types of nerve injuries (peripheral versus spinal nerve, ligation versus chronic constrictive injury) have persistently implicated a pivotal role for TNF-alpha at both peripheral and central levels of sensitization. Despite a lack of success in clinical trials of anti-TNF-alpha therapy in alleviating the sciatic type of neuropathic pain, the intricate link of TNF-alpha with other neuro-inflammatory signaling systems (e.g., chemokines and p38 MAPK) has indeed inspired a systems approach perspective for future drug development in treating neuropathic pain.


Figure 1
Figure 1
The roles of TNF-α as recognized at different levels of the nervous system in neuropathic pain induced by nerve injury: (1) at site of nerve injury; (2) at dorsal root ganglion; (3) at dorsal horn of the spinal cord; and (4) at the brain and higher centres.

Similar articles

See all similar articles

Cited by 128 PubMed Central articles

See all "Cited by" articles


    1. Campbell JN, Meyer RA. Mechanisms of neuropathic pain. Neuron. 2006;52:77–92. doi: 10.1016/j.neuron.2006.09.021. - DOI - PMC - PubMed
    1. McMahon SB, Cafferty WB, Marchand F. Immune and glial cell factors as pain mediators and modulators. Exp Neurol. 2005;192:444–462. doi: 10.1016/j.expneurol.2004.11.001. - DOI - PubMed
    1. Marchand F, Perretti M, McMahon SB. Role of the immune system in chronic pain. Nat Rev Neurosci. 2005;6:521–532. doi: 10.1038/nrn1700. - DOI - PubMed
    1. Moalem G, Tracey DJ. Immune and inflammatory mechanisms in neuropathic pain. Brain Res Rev. 2006;51:240–264. doi: 10.1016/j.brainresrev.2005.11.004. - DOI - PubMed
    1. Bowsher D. Neurogenic pain syndromes and their management. Br Med Bull. 1991;47:644–666. - PubMed

MeSH terms